Contact investigation for tuberculosis: a systematic review and meta-analysis

Abstract

Investigation of contacts of patients with tuberculosis (TB) is a priority for TB control in high-income countries, and is increasingly being considered in resource-limited settings. This review was commissioned for a World Health Organization Expert Panel to develop global contact investigation guidelines. We performed a systematic review and meta-analysis of all studies reporting the prevalence of TB and latent TB infection, and the annual incidence of TB among contacts of patients with TB. After screening 9,555 titles, we included 203 published studies. In 95 studies from low- and middle-income settings, the prevalence of active TB in all contacts was 3.1% (95% CI 2.2-4.4%, I(2)=99.4%), microbiologically proven TB was 1.2% (95% CI 0.9-1.8%, I(2)=95.9%), and latent TB infection was 51.5% (95% CI 47.1-55.8%, I(2)=98.9%). The prevalence of TB among household contacts was 3.1% (95% CI 2.1-4.5%, I(2)=98.8%) and among contacts of patients with multidrug-resistant or extensively drug-resistant TB was 3.4% (95% CI 0.8-12.6%, I(2)=95.7%). Incidence was greatest in the first year after exposure. In 108 studies from high-income settings, the prevalence of TB among contacts was 1.4% (95% CI 1.1-1.8%, I(2)=98.7%), and the prevalence of latent infection was 28.1% (95% CI 24.2-32.4%, I(2)=99.5%). There was substantial heterogeneity among published studies. Contacts of TB patients are a high-risk group for developing TB, particularly within the first year. Children <5 yrs of age and people living with HIV are particularly at risk. Policy recommendations must consider evidence of the cost-effectiveness of various contact tracing strategies, and also incorporate complementary strategies to enhance case finding.

Figure 1–

Flow diagram for study selection. TB: tuberculosis; LTBI: latent tuberculosis infection.

Figure 2–

Annual incidence rate of tuberculosis (TB) in contacts by year of follow-up, according to country income. World Bank Income Gross National Income per capita: low income (≤$1,005 per yr); lower-middle income ($1,006 to $3,975 per yr); upper-middle income ($3,976 to $12,275 per yr); high income (≥$12,276 per yr) [22]. *: p<0.05, statistically significant difference between contacts from high compared to low–middle-income countries. ^#: [, , –, –, –, –193]; ^¶: [, , –, , , , , , , –, , , , , , –202]. Refer to the supplementary material for complete details of outcomes, estimates of heterogeneity and outcomes of individual included studies.

Figure 3–

Forest plot of the prevalence of active tuberculosis (TB) among contacts of smear-positive TB in low–middle-income countries. The size of the symbols is proportional to the study sample size.

Figure 4–

Forest plot of the prevalence of active tuberculosis (TB) among contacts of smear-positive TB in high-income countries. The size of the symbols is proportional to the study sample size.